Plasma Concentrations and Beta-Blocking Effects in Normal Volunteers After Intravenous Doses of Metoprolol and Propranolol

1. Dopamine and prostaglandins are putative endogenous natriuretic hormones. The role of each in facilitating natriuresis induced by intravenous saline infusion was examined in normal volunteers in relation to administration of carbidopa, a dopadecarboxylase inhibitor, and indomethacin, an inhibitor of prostaglandin synthetase. 2. In a placebo-controlled, randomized study, 13 subjects received carbidopa (100 mg) and 12 received indomethacin (50 mg). Proximal and distal renal tubular Na+ reabsorption were determined using exogenous lithium clearance. 3. On the control day, 2 litres of 0.9% saline (308 mmol Na+) given intravenously in 3 h, resulted in volume expansion and natriuresis. Carbidopa reduced the urinary dopamine/noradrenaline ratio but showed no anti-natriuretic effect and no effect on fractional Na+ reabsorption. Indomethacin diminished natriuresis and increased distal fractional Na+ reabsorption in proportion to the anti-natriuretic effect. 4. The changes in plasma concentrations of albumin, aldosterone, atrial natriuretic peptide and renin activity associated with volume expansion were not modified by either carbidopa or indomethacin. Urinary prostaglandin E2 excretion was decreased transiently by indomethacin and was unaffected by carbidopa. 5. This study suggests that prostaglandins may modulate urinary Na+ excretion during saline-induced natriuresis through inhibition of distal tubular Na+ reabsorption. No role for free dopamine as a modulator of renal Na+ handling could be assigned on the basis of the findings with carbidopa.

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Differences between beta-blocking effects of metoprolol, bisoprolol and carvedilol

Clinical Pharmacology & Therapeutics ◽

10.1016/s0009-9236(03)90588-1 ◽

2003 ◽

Vol 73 (2) ◽

pp. P62-P62

Author(s):

G. Koshucharova ◽

K. Stoschitzky ◽

W. Klein

Keyword(s):

Blocking Effects ◽

Beta Blocking

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EVALUATION OF THE NATRIURETIC AND BETA-ADRENOCEPTOR-BLOCKING EFFECTS OF TIENOXOLOL IN NORMAL VOLUNTEERS

Fundamental and Clinical Pharmacology ◽

10.1111/j.1472-8206.1988.tb01009.x ◽

1988 ◽

Vol 2 (5) ◽

pp. 441-454 ◽

Cited By ~ 4

Author(s):

A. BERDEAUX ◽

E. LOUESLATI ◽

J.L. GERARD ◽

E. PUSSARD ◽

J.F. GIUDICELLI

Keyword(s):

Normal Volunteers ◽

Beta Adrenoceptor ◽

Blocking Effects

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Differing beta-blocking effects of carvedilol and metoprolol

European Journal of Heart Failure ◽

10.1016/s1388-9842(01)00126-x ◽

2001 ◽

Vol 3 (3) ◽

pp. 343-349 ◽

Cited By ~ 20

Author(s):

Kurt Stoschitzky ◽

Gergana Koshucharova ◽

Robert Zweiker ◽

Robert Maier ◽

Norbert Watzinger ◽

...

Keyword(s):

Blocking Effects ◽

Beta Blocking

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Pharmacokinetics and beta-blocking effects of timolol in poor and extensive metabolizers of debrisoquin

Clinical Pharmacology & Therapeutics ◽

10.1038/clpt.1985.195 ◽

1985 ◽

Vol 38 (4) ◽

pp. 409-413 ◽

Cited By ~ 44

Author(s):

John C McGourty ◽

Joseph H Silas ◽

Jude J Fleming ◽

Alan McBurney ◽

John W Ward

Keyword(s):

Extensive Metabolizers ◽

Blocking Effects ◽

Beta Blocking

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Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol

Cardiology ◽

10.1159/000093060 ◽

2006 ◽

Vol 106 (4) ◽

pp. 199-206 ◽

Cited By ~ 42

Author(s):

Kurt Stoschitzky ◽

Gergana Stoschitzky ◽

Helmut Brussee ◽

Claudia Bonell ◽

Harald Dobnig

Keyword(s):

Blocking Effects ◽

Beta Blocking

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Determination of metanephrines in plasma by liquid chromatography with electrochemical detection

Clinical Chemistry ◽

10.1093/clinchem/39.1.97 ◽

1993 ◽

Vol 39 (1) ◽

pp. 97-103 ◽

Cited By ~ 116

Author(s):

J W Lenders ◽

G Eisenhofer ◽

I Armando ◽

H R Keiser ◽

D S Goldstein ◽

...

Keyword(s):

Liquid Chromatography ◽

Electrochemical Detection ◽

Plasma Concentrations ◽

Reversed Phase ◽

Assay Method ◽

Normal Volunteers ◽

Cation Exchange Column ◽

Extraneuronal Metabolism ◽

Mn Concentrations

Abstract Metanephrines are O-methylated metabolites of catecholamines. We report the use of liquid chromatography with electrochemical detection to determine plasma concentrations of normetanephrine (NMN) and metanephrine (MN). Plasma NMN and MN in 32 normal volunteers and inpatients were compared with concentrations in 23 patients with pheochromocytoma. Metanephrines were adsorbed from plasma onto a cation-exchange column and eluted with ammoniacal methanol. The dried residue was dissolved in mobile phase and injected onto a reversed-phase column. Recoveries of NMN and MN from 1 mL of plasma averaged 50-70%, and results varied linearly with quantity injected over a range of 0.13-55 pmol. The detection limit was 25 fmol for NMN and 50 fmol for MN. Intra-assay CVs were < 5%. In normal volunteers and inpatients, plasma concentrations of NMN ranged between 0.12 and 0.73 nmol/L (mean 0.38 nmol/L), and MN between 0.06 and 0.63 nmol/L (mean 0.19 nmol/L). Plasma NMN concentrations were increased in all 23 patients with pheochromocytoma (range 1-172 nmol/L), whereas MN concentrations (range 0.10-382 nmol/L) were increased in only 9 patients. The assay method is reliable and sensitive and offers an approach to examine the extraneuronal metabolism of catecholamines. The method may also be useful in the diagnosis of pheochromocytoma.

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